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1
Höök, Josef. "Multispectral auroral imager and optical flow in aurora." Thesis, KTH, Rymd- och plasmafysik, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-91893.
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”Auroral Structure and Kinetics” (ASK) is a multispectral auroral imager,developed and built by University of Southampton, UK, and Royal Institute ofTechnology, Sweden. The scientific objective of the instrument include characterisationof both high and low energy electron precipitation in aurora with highspatial and temporal resolution, and direct observation of plasma drifts in theionosphere. ASK consists of three cameras taking images in different spectrallines. One part of this thesis deals with the development of the data acquisitionsystem for the instrument. This included the hardware part (computers controllingthe cameras)and the software for operation of ASK. ASK was installedon Svalbard in November 2005, and examples of first data are presented. Thesecond part of the thesis treats the problem of estimation of motions from theauroral sequences. Robust optical flow estimation algorithm has been applied toauroral sequences, and new formulations specific to the imaging of metastableions (carried out by ASK) are suggested.
2
Álvarez, García Daniel, Salazar Enrique Alberto Cebreros, Ludeña Yenifer Carolina Herrera, Vásquez María Angélica Herrera, and Monrroy Mariafe Jazmín Sayas. "Proyecto Aurora." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2021. http://hdl.handle.net/10757/655422.
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En el presente trabajo de investigación se analizan todos los aspectos necesarios para iniciar un proyecto de negocio basado en la elaboración y comercialización de productos de cuidado personal hechos a base de algas pardas, mayormente conocido como sargazo. Este insumo brinda colágeno, hidrata y contiene vitaminas beneficiosas para la piel, por lo que es adecuado recibir sus nutrientes a través de productos de uso rutinario.
Actualmente, el mercado de productos de higiene y cuidado personal se encuentra en crecimiento por la situación actual de la pandemia del COVID-19, por lo que la población ha priorizado el consumo de productos que le aseguren limpieza y cuidado. Adicionalmente, ya existía una tendencia a utilizar productos que contengan insumos naturales para el cuidado de la piel, por lo que un negocio con estas características tiene valor agregado frente a las otras empresas del mercado actual en Perú.
A partir de las situaciones planteadas nace Aurora, negocio de productos de cuidado personal hechos a base de algas pardas en presentación de jabón y crema hidratante. Aurora cubre las necesidades de este tipo de productos de los usuarios de nivel socioeconómico A/B y C de las zonas 6 y 7 de Lima Metropolitana. Se estima que su tamaño de mercado inicialmente es de 432 649 personas, con un crecimiento anual del 6%. Para el inicio de sus operaciones se necesita una inversión inicial de S/ 14 869,26, la cual le permitirá adquirir los recursos necesarios para la producción y comercialización del producto.This research work analyzes all the necessary aspects to start a business project based on the development and commercialization of personal care products made from brown algae, mostly known as sargassum. This input provides collagen, hydrates and contains beneficial vitamins for the skin, so it is appropriate to receive its nutrients through products for routine use. Currently, the market for hygiene and personal care products is growing due to the current situation of the COVID-19 pandemic, so the population has prioritized the consumption of products that ensure cleanliness and care. Additionally, there was already a tendency to use products that contain natural ingredients for skin care, so a business with these characteristics has added value compared to other companies in the current market in Peru. From the situations raised, Aurora was born, a business of personal care products made from brown algae in a presentation of soap and moisturizer. Aurora covers the needs of this type of product for users of socioeconomic levels A / B and C in zones 6 and 7 of Metropolitan Lima. It is estimated that its market size initially is 432 649 people, with an annual growth of 6%. An initial investment of S / 14,869.26 is required to start its operations, which will allow it to acquire the necessary resources for the production and commercialization of the product.
Trabajo de investigación
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Ireland, Ryan Patrick. "Beyond Aurora." Wright State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1308585211.
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Mu, Jun. "VHF radar aurora, statistics, fading and correlation with optical aurora." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1996. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq24039.pdf.
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Poynton, Michelle Bella D. "The Aurora project." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/4724.
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Gil, Sánchez Jorge Luis, and Cavero Iván Artemio Janqui. "Proyecto Multifamiliar Aurora." Master's thesis, Pontificia Universidad Católica del Perú, 2018. http://hdl.handle.net/20.500.12404/14372.
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La presente tesis desarrolla el estudio de mercado y la propuesta de producto para un
edificio multifamiliar ubicado en el Distrito de Miraflores, en una de las zonas mejor
valoradas de Lima para uso residencial.
Durante el periodo 2017-2018 se ha producido una reactivación del mercado inmobiliario
frente al cual nuestro proyecto se busca posicionar como una opción de calidad y al
mismo tiempo de una baja relación costo-beneficio en relación a los productos de la
competencia dentro de este sector denominado Lima Top. Este sector siempre presenta
una demanda estable, que durante el último periodo se ha incrementado en un 25% y
además ha madurado en cuanto a su elección en la compra de inmuebles.
Entre los atributos de nuestros productos, entregamos al cliente una alta calidad en el
diseño acorde a las exigencias de este sector y dentro de la propuesta de diseño, la
flexibilidad de la distribución la cual permite obtener productos con menores precios,
igual equipamiento y mismo número de ambientes. Con estas características y
considerando los precios de venta, costo de construcción y velocidad de ventas
estimadas en la zona, consideramos nuestro proyecto como una oportunidad de negocio
rentable y de mejora al urbanismo de la zona.
Para lograr este propósito, se hace un estudio situacional a nivel económico social del
país y la región, para identificar amenazas y oportunidades en el macroentorno. Luego
en el estudio de mercado se muestran las características de la competencia en cuanto
al detalle de sus diseños, sus precios y sus velocidades de venta, a fin de conocer que
es lo que más valora la demanda de este sector.
Luego de conocer estas preferencias, se realiza el diseño y cabida preliminar del
producto, basado en las restricciones urbanísticas y de mercado de la zona. En esta
etapa se encuentra un factor de costo de terreno vs venta adecuada. En ese sentido el
producto resultante consiste en un proyecto de 10 departamentos: 8 flats del primer al
cuarto nivel; y 2 dúplex ubicados en el quinto nivel y azotea. Se cuenta con 10 depósitos
y 33 estacionamientos ubicados en el semisótano, sótano 1 y sótano 2. En los flats del
primer piso, se ha generado una sala de reunión ubicada en el semisótano y en los pisos
ubicados entre el primer, segundo, tercero y cuarto nivel, se ha propuesto la posibilidad
de convertir el walking closet del dormitorio principal en un tercer dormitorio para la
vivienda.
Basado en la valoración de nuestra competencia encontramos una oportunidad de
ingresar a través del posicionamiento de un producto con una baja relación costo-beneficio, lo cual es y transmitido al cliente mediante nuestro marketing mix como el
hecho que nuestros precios de venta totales son menores en un 30% en un
departamento con igual equipamiento en menor área construida y mejor distribución.
Una vez definido el producto y la forma de ingresarlo al mercado, procedemos a realizar
el análisis económico y financiero en la cual el escenario base, considera una velocidad
de venta promedio estimada de una (1) unidad por mes. Sometido a distintas
condiciones mediante el análisis de sensibilidad, el proyecto resulta con un VAN positivo
hasta una variación de velocidad de venta hasta 0.4 unidades por mes y el costo de
construcción puede subir hasta un máximo de 32.16% para resultar con un VAN positivo.
Y respecto al flujo financiero del proyecto, resulta un VAN financiero mayor al VAN del
flujo de caja operativo, lo que demuestra que la gestión financiera está agregando valor
al proyecto.
Bajo la gestión del proyecto y los cambios en las variables más incidentes en el
escenario más pesimista, el proyecto nos resulta con un VAN positivo, lo que demuestra
que el proyecto agregará valor al inversionista de manera segura.Tesis
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Alcócer, Gamarra Alex, Ostolaza Sandra Ascenzo, Ingunza Rodolfo Mendoza, Mendoza Carola Pacheco, and Guerra Marietta Ramírez. "Edificio Multifamiliar: Aurora I." Universidad Peruana de Ciencias Aplicadas - UPC. Escuela de Postgrado, 2009. http://hdl.handle.net/10757/273964.
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El presente estudio tiene la finalidad de determinar la rentabilidad de nuestro tercer proyecto inmobiliario, el Multifamiliar Aurora I, ubicado en el distrito de Miraflores, en la esquina de la calle García Gastañeta y la Avenida Villarán La primera parte del estudio permite determinar el Estado de Pérdidas y Ganancias estimado del proyecto inmobiliario; para la elaboración de este reporte se ha realizado un estudio técnico del costo de inversión en todas sus etapas, así como un estudio de la oferta existente en la zona La segunda parte del estudio consistirá en elaborar el Análisis Financiero, determinando la viabilidad y rentabilidad del proyecto y las alternativas de financiamiento Así mismo, se elaborará un Plan de Marketing basado en el estudio de mercado y el análisis del sector, para asegurar de esta manera la venta de los departamentos en los plazos requeridos
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Santos, Edmilson Ozorio dos. "Investigação das quinases Aurora A e Aurora B na tumorigenicidade mediada pelo oncogene KRAS." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-21062017-103949/.
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O câncer de pulmão é a principal causa de morte relacionada ao câncer no mundo. Mutações em KRAS são altamente prevalentes no câncer e têm sido diretamente associadas ao processo tumorigênico. Apesar disso, até hoje todas as terapias visando inibir KRAS diretamente falharam e a caracterização de alvos indiretos, importantes para a oncogênese mediada por KRAS, é fundamental para o desenvolvimento de novas terapias contra o câncer de pulmão. Nós mostramos previamente que as quinases Aurora A (AURKA) e B (AURKB) são alvos a jusante de KRAS, importantes para o crescimento, viabilidade e oncogenicidade de linhagens celulares derivadas de tumores pulmonares mediados por KRAS. Aqui, nós aprofundamos os nossos estudos para melhor caracterizar AURKA e AURKB como potenciais alvos terapêuticos no câncer de pulmão. Os objetivos deste trabalho foram (1) investigar o mecanismo de perda de viabilidade induzido pela inibição de AURKA e/ou AURKB; (2) avaliar como a inibição de AURKA e/ou AURKB afeta propriedades oncogênicas relacionadas à agressividade tumoral; e (3) como a inibição destas quinases afeta o crescimento tumoral in vivo. Para tanto, nós utilizamos dois modelos celulares: (1) células A549 e H358, que apresentam mutações em KRAS, geneticamente modificadas para a expressão estável e induzível de shRNAs contra AURKA ou AURKB, e (2) células tumorais H1703, que não apresentam mutações em KRAS, geneticamente modificadas para a expressão induzível de KRASG12V, tratadas ou não com inibidores farmacológicos das quinases Aurora. A inibição farmacológica ou por interferência de RNA de AURKA e/ou AURKB em células H358 e A549 reduziu a proliferação celular, sendo esta inibição acompanhada de anomalias mitóticas, além de aneuploidia e poliploidia. A inibição destas quinases também induziu morte celular in vitro, tanto em mitose, quanto em interfase. Mais interessantemente, a inibição farmacológica dual de AURKA e AURKB induziu morte celular in vitro em células H1703, somente na presença de KRASG12V, indicando que a inibição das quinases Aurora afeta preferencialmente células portadoras de mutações em KRAS. Além disso, a inibição de AURKA e/ou AURKB reduziu propriedades malignas celulares relacionadas à agressividade tumoral, como migração, invasão e adesão. Finalmente, a inibição de AURKA por RNA de interferência em células A549 também reduziu a formação de tumores in vivo. Entretanto, como a inibição destas quinases levou a anomalias mitóticas e à instabilidade genética, nós resolvemos investigar se a inibição de TPX2, um substrato e ativador de AURKA, poderia ser uma abordagem alternativa para inibir esta via em câncer de pulmão induzido por KRAS. Primeiramente, nós observamos nos nossos modelos celulares que KRAS regula positivamente a expressão de TPX2. Além disso, a inibição de TPX2 em células pulmonares portadoras de KRAS oncogênica reduziu a viabilidade e proliferação celulares e induziu morte celular. Mais interessantemente, esses efeitos ocorreram preferencialmente em células que expressam KRAS oncogênica. Em conclusão, nossos resultados apoiam a hipótese de que a ativação de AURKA/TPX2 e AURKB por KRAS são eventos importantes no câncer de pulmão e sugerem a inibição destas vias, possivelmente em combinação com outras terapias citotóxicas, como uma nova abordagem terapêutica para o câncer de pulmão induzido por KRAS.Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS mutations are widespread in lung cancer and have been causally linked to tumorigenesis. Nonetheless, therapies targeting KRAS directly have so far failed and characterization of indirect KRAS targets, which play important roles in KRAS-mediated oncogenesis, is crucial for the development of new therapies for lung cancer. We have previously shown that mitotic kinases Aurora A (AURKA) and B (AURKB) are downstream targets of oncogenic KRAS, important for the growth, viability, and oncogenicity of KRAS-transformed lung cancer cell lines. Here, we studied these kinases more in depth in order to better characterize them as potential therapeutical targets for KRAS-induced lung cancer. The aims of this study were (1) to investigate the mechanism leading to loss of viability upon AURKA and/or AURKB targeting; (2) to evaluate how AURKA and/or AURKB inhibition affects malignant properties associated with tumor aggressiveness; and (3) to determine whether AURKA and/or AURKB inhibition reduces KRAS-induced tumor growth in vivo. For that purpose, we used two cell-based models: (1) KRAS mutant A549 and H358 cells with stable and inducible shRNA-mediated knockdown of AURKA or AURKB, and (2) KRAS wildtype H1703 tumor cell lines, genetically engineered to inducibly express oncogenic KRASG12V treated or not with Aurora kinase pharmacological inhibitors. Targeting AURKA and/or AURKB pharmacologically or by RNA interference in H358 and A549 cells led to decreased cell proliferation, which was accompanied by mitotic abnormalities, leading to aneuploidy and hyperploidy. Aurora kinase targeting also induced cell death in vitro, both during mitosis and interphase. More importantly, AURKA and AURKB inhibition with a dual pharmacological inhibitor in H1703 cells induced cell death in vitro, but only in the presence of KRASG12V, indicating that Aurora kinase targeting affects preferentially lung cells harboring oncogenic KRAS. Furthermore, AURKA and/or AURKB targeting reduced malignant properties associated with tumor aggressiveness, such as cell migration, invasion and adhesion. Finally, AURKA targeting by RNA interference in A549 cells also reduced growth of xenograft tumors in vivo. Nonetheless, since Aurora targeting was associated with mitotic abnormalities and genetic instability, we decided to investigate if targeting TPX2, a substrate and an activator of AURKA, could constitute an alternative approach to targeting this pathway in KRAS-induced lung cancer. First, using our cell-based models, we determined that KRAS positively regulates TPX2 expression. In addition, TPX2 inhibition by RNA interference in KRAS-positive lung cells reduced cell viability and proliferation and induced cell death. Finally, these effects occurred preferentially in cells harboring oncogenic KRAS. In conclusion, our results support the hypothesis that activation of AURKA/TPX2 and AURKB by KRAS are important events in lung cancer and suggest inhibition of these pathways, possibly in combination with other cytotoxic therapies, as a new approach for KRAS-induced lung cancer therapy.
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Coe, Godfrey. "Radar studies of the aurora." Thesis, University of Leicester, 1985. http://hdl.handle.net/2381/35859.
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The investigation of the high-latitude aurora by means of the V.H.F. auroral radar SABRE, (Swedish And British auroral Radar Experiment), developed by the Leicester University Ionospheric Physics group, is described. The first two chapters review previous studies of the atmosphere by radar techniques and includes a description of the SABRE radar. The basic radar equation and velocity relationships are derived and the various loss factors examined. From analysis of the echo signal data for the diffuse aurora, and examination of signal data from a radio star, the SABRE radar parameters are established. An investigation is then undertaken of the variation of the electrojet parameters, (derived from application of the radar equation to the SABRE data), with height, electric field strength and geomagnetic conditions. Evidence is found of backscattering from irregularities generated by both two-stream and gradient drift processes. An examination is also made of the echo signals detected at relatively short ranges, of below 370 km, and several causal mechanisms are investigated including scattering processes in the neutral atmosphere. It is evident that aircraft are predominantly the cause of these short-range echoes. This investigation also reveals a number of software and hardware faults in the initial radar configuration. This Thesis is concluded with suggestions for future development of the radar system, which include the implementation of a height-finding facility and improved spectral resolution.
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Soto, Gallupe Jhonny. "Proyecto inmobiliario edificio Parque Aurora." Universidad Peruana de Ciencias Aplicadas - UPC. Escuela de Postgrado, 2010. http://hdl.handle.net/10757/274026.
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El proyecto inmobiliario al que se refiere el presente documento, nace en un entorno bastante favorable, quedando supeditado sus resultados únicamente al desempeño de la organización que la llevará adelante, lo que en buena medida importa la optimización de las decisiones de los cuadros directivos e igualmente el cabal desempeño de los miembros de la organización a todos sus niveles Esto último en buena cuenta garantizará en gran medida el éxito del proyecto
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Williams, John Denis. "An investigation into pulsating aurora /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/6820.
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Retherford, Kurt D. "Io's aurora HST/STIS observations /." Available to US Hopkins community, 2002. http://wwwlib.umi.com/dissertations/dlnow/3068201.
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André, Mattias, Nikola Mrdjanov, and John Seliö. "Optimering av hybriddrift för Aurora." Thesis, KTH, Maskinkonstruktion (Inst.), 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-171979.
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Tävlingen Eco Marathon som årligen arrangeras av Shell har som mål att utnyttja studenters innovations- och kreativitet för att ta fram konceptbilar med minsta möjliga bränsleförbrukning. Målet med projektet har varit att ta fram en optimerad hybriddrift för en framtida version av Aurora som tävlar i Urban Concept klassen. Denna ska även innehålla regenerativa bromsar som tar tillvara på rörelseenergin vid inbromsningarna. Först gjordes en litteraturstudie och två koncept togs fram för vidare utvärdering. Dessa har sedan utvärderats med hjälp av programmet Simulink som är en del av MATLAB. Stor vikt har lagts vid konstruktionen av dessa simuleringsmodeller för att få dem korrekta. Målet för optimeringen har varit att få den totala bränsleförbrukningen under en simulerad tävling så låg som möjligt. Rekommendationen för en framtida version av Aurora är att använda sig av det parallellhybridskoncept som beskrivs på sida 16 i denna rapport. En elmotor används för att accelerera och bromsa bilen medan förbränningsmotorn driver bilen vid konstant marschhastighet. Tanken med detta koncept har varit att minimera förlusterna vid omvandling av energi. Vid jämförelsen mellan de båda koncepten upptäcktes att parallellhybriden hade en förbrukning som var 4-5 % lägre än en seriehybrid för alla olika driftsförhållanden. Vid simuleringen har en körstil optimerad för just Eco marathon använts och ingen variation av denna har gjorts. Förluster i växlar och liknande har inte behandlats vid simuleringarna då dessa inte har varit relevanta för jämförelsen. Dessa förluster kan dock enkelt inkluderas i modellerna om så önskas. Den enskilda parameter som påverkade bränsleförbrukningen mest var verkningsgraden hos förbränningsmotorn. Däremot var rullmotståndet för bilen en viktig parameter. Vid en fördubbling av rullmotståndet ökade bränsleförbrukningen med 50 %. Rullmotståndet påverkas både av rullfriktionen och av vikten hos fordonet, det är alltså av yttersta vikt att göra bilen så lätt som möjligt. Den regenerativa bromsningen fungerar genom att motorns styrelektronik tar ut en ström ur motorn och transformerar upp spänningen till den aktuella kondensatorspänningen. Vid bromsning från marschfart återvinns ca 70 % av rörelseenergin, tillräckligt för en halv minuts körning vid marschfart eller acceleration upp till 21 km/h. Den regenerativa bromsningen gav en relativt liten fördel men vinsten ökar ju oftare bilen ska bromsas och accelereras.The goal of this project has been to develop a new hybrid driveline concept, including regenerative braking, for a future version of KTH’s latest Eco-car. The car, Aurora, competes in the urban concept class of Shell Eco-marathon. Students from universities all over the world struggle to race their specially built cars a set distance on the least amount of fuel. In the urban concept class the cars are required to resemble road vehicles to at least some degree. The new driveline should also make use of regenerative braking so that the car’s kinetic energy can be recovered and stored in the vehicle’s super-capacitor. At first, recent literature on the subject of hybrid vehicles and work on Aurora’s predecessor Spiros was studied. With the knowledge of advantages and drawbacks of existing drivelines, two concepts were chosen for further evaluation. These concepts were then modeled in Simulink and simulations were carried out where various parameters were changed in order to maximize fuel efficiency. Great effort has been put into these models to make them as accurate and valid as possible. The recommendation on upgrading the Aurora for its next version is to use the parallel-hybrid driveline concept described on page 16. An electric motor is used to accelerate the car to a designated speed since an electric motor is the most efficient at providing torque at low speeds. After accelerating, an internal combustion engine will power the car. The two main advantages of this system is that energy conversion losses are kept at a minimum, and that the internal combustion engine will operate only at its optimal speed and power, resulting in maximized efficiency. In simulations, the fuel consumption of the parallel driveline was consistently found to be 4-5 % lower than that of the series-hybrid driveline. None of the dynamics in the gasoline engine have been modeled or studied. Its efficiency has been assumed to be constant in the narrow operating range in which the motor is used. Engine efficiency is the most critical factor for achieving low overall fuel consumption. One of the other parameters that influenced fuel consumption the most was rolling resistance. When doubled it would increase the fuel consumption by 50 %. The rolling resistance depends on the rolling resistance coefficient and the total weight of the car.Regenerative braking was able to recover about 70 % of the kinetic energy during an average stop, enough to run the car for half a minute at cruising speed or accelerate the car to 21 km/h. The advantage of regenerative braking was relatively small but would increase if more stops were required during the race.
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Dias, Geraldo Pereira [UNIFESP]. "Aurora: uma obra de transição na filosofia de Nietzsche?" Universidade Federal de São Paulo (UNIFESP), 2013. http://repositorio.unifesp.br/handle/11600/39294.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
No presente trabalho, temos por objetivo analisar a hipótese de que o livro Aurora, no conjunto dos escritos de Friedrich Nietzsche, mostra-se como uma obra de transição. Nesse livro, mostraremos que Nietzsche começa a criar um quadro teórico que lhe possibilitará desenvolver temas centrais de sua filosofia. Com essa interpretação, faremos ver que, justamente por causa desse caráter transitório, essa obra tem sido tão subestimada. Atualmente Aurora suscita um interesse renovado na pesquisa internacional sobre Nietzsche; ainda sim, muitas vezes nos depararmos com leituras que tendem a desconsiderar seu caráter transitório, e, por isso mesmo, acabam por obscurecê-la. Isso tem ocorrido sempre que os comentadores interpretam Aurora à luz de conceitos, projetos e doutrinas filosóficas posteriores ao livro. Para nos contrapor a essa literatura que tende a submeter Aurora à filosofia tardia de Nietzsche, pretendemos analisá-la em seu tempo próprio, única maneira de verificar em que sentido as ideias presentes no livro contribuíram para viabilizar a construção de conceitos tais como genealogia, vontade de potência e transvaloração dos valores.
In this work, we aim to examine the hypothesis that the book Daybreak, in all the writings of Friedrich Nietzsche, shows up as a transitional work. In this book, we will show that Nietzsche begins to create a theoretical framework that will enable you to develop the central themes of his philosophy. With this interpretation, we see that, precisely because of this character transitive, this work has been so underestimated. Currently Daybreak raises renewed interest in international research on Nietzsche; yet, often we encounter readings that tend to disregard their transitory character, and, therefore, end up obscuring it. This has occurred whenever the commentators interpret Daybreak through of the concepts, designs and philosophical doctrines after the book. To counter this in the literature tends to refer to the Daybreak later philosophy of Nietzsche, we intend to analyze it on your own time, the only way to check which way the ideas presented in the book contributed to enable the construction of the concepts such as genealogy, will to Power and Re-evaluation of Values.
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Lioutas, Antonio 1980. "Aurora A kinase function during anaphase." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/97290.
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Aurora A (AurA) is an important mitotic kinase mainly studied for its
involvement in cell cycle progression, centrosome maturation,
mitotic spindle pole organization and bipolar spindle formation. It
localizes to duplicated centrosomes and spindle microtubules (MTs)
during mitosis where it regulates various factors participating in
metaphase spindle formation. AurA is degraded late in mitosis
suggesting that it might also have a function in anaphase. In this
study we focused in understanding AurA function during anaphase
in two different experimental systems.
First, we kept AurA active in cycled Xenopus egg extracts and found
that MTs maintained their mitotic organization longer throughout
mitotic exit. We also observed chromosome segregation defects and
problematic nuclear envelope formation. These observations
indicate that AurA activity needs to be down-regulated for the
transition from metaphase back to interphase.
To get insights into the role of AurA during metaphase-anaphase
transition we initially asked whether its kinase activity is still
necessary for the maintenance of the metaphase spindle. We saw
that the inhibition of AurA kinase activity in metaphase resulted to a
collapse of the established metaphase spindle in HeLa cells.
Indicating that AurA activity is necessary for the metaphase spindle
maintenance.
Then, we looked whether AurA kinase activity is still necessary
during anaphase. We inhibited AurA at the onset of anaphase in
Hela cells and found that anaphase spindles were smaller. We also
observed that the MT structure responsible for anaphase spindle
elongation, the central spindle, was defectively assembled and
organized. Moreover, in cells where AurA was inhibited segregation
of chromosomes was defective. These results indicate that AurA
kinase activity is necessary for anaphase spindle elongation, central
spindle assembly and organization and chromosome segregation.
To understand further how AurA regulates anaphase spindle
formation we looked known AurA substrates. We depleted TACC3,
a known AurA substrate involved in MT formation earlier in mitosis
and observed that TACC3 depletion phenocopied AurA inhibition.
This indicates that TACC3 has a function in MT organization and
chromosome segregation during anaphase and this function could
possibly be regulated by AurA.
In this study we have demonstrated that AurA activity is essential for
metaphase spindle maintenance. We also found that during
anaphase when AurA is either maintained active or inhibited MT
organization is greatly affected and chromosome segregation is
defective. Suggesting that AurA activity needs to be tightly controlled
during anaphase for a correct completion of mitosis.Aurora A (AurA) es una quinasa mitótica importante que se ha estudiado principalmente en su papel durante la progresión del ciclo celular, la maduración del centrosoma, la organización y la formación del polo y del huso mitótico. Durante la mitosis, AurA se localiza en los centrosomas duplicados y en los microtúbulos (MTs) del huso y se ha observado que regula varios factores que participan en la formación del huso mitótico. AurA se degrada al final de la mitosis indicando que pueda tener una función durante la anafase. En este estudio nos hemos centrado en la comprensión de la función de AurA durante la anafase en dos sistemas experimentales diferentes. En primer lugar, utilizando extractos de huevos de Xenopus hemos mantenido AurA activa durante la transición de metafase a anafase y hemos visto que los MTs del huso mitótico mantienen su organización durante más tiempo. También hemos observado que cuando AurA se mantiene activa existen defectos en la segregación cromosómica y la formación de la membrana nuclear. Esto indica que la actividad de AurA tiene un papel regulador sobre los MTs y la chromatina durante la transición de la metafase a la interfase. Para entender cual es la función de AurA durante la transición de metafase a anafase primero hemos estudiado si la actividad de la quinasa es necesaria para el mantenimiento del huso mitótico. Hemos visto que la inhibición de la actividad quinasa AurA resultó en el colapso del huso durante la metafase en células HeLa. Esto indica que la actividad de AurA es necesaria para el mantenimiento del huso mitótico de metafase. A continuación hemos analizamos si la actividad quinasa de AurA sigue siendo necesaria para la anafase. Para ello hemos inhibido AurA en células Hela al inicio de la anafase. En estas condiciones los husos de la anafase son más pequeños y la estructura de los MTs responsable del alargamiento del huso mitótico durante la anafase, el huso central, se organiza defectuosamente. Además, se encontraron errores durante la segregación de los cromosomas. Estos resultados indican que la actividad quinasa de AurA es necesaria para el alargamiento del huso durante la anafase y la organización y segregación cromosómica. Para entender el mecanismo de la función de AurA durante la anafase hemos estudiado a sustratos de AurA. Al estudiar TACC3 , un sustrato conocido de AurA que participa en la formación de MTs en las fase iniciales de la mitosis hemos encontrado que su eliminación de células HeLa produce el mismo fenotipo que la inhibición de AurA. Esto indica que TACC3 tiene una función en la organización de MT y la segregación de cromosomas durante la anafase y que esta función podría estar regulada por la quinasa AurA. En este estudio hemos demostrado que la actividad quinasa de AurA es esencial para el mantenimiento del huso mitótico. También hemos encontrado que durante la anafase cuando la quinasa AurA se mantiene activa o se inhibe la organización de los MTs del huso mitótico se ve muy afectada y los cromosomas se segregan defectuosamente. Por tanto los resultados de este estudio indican que la actividad quinasa de AurA está estrechamente controlada durante la anafase para el correcto cumplimiento de la mitosis.
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Jackel, Brian J. "Spectral characteristics of UHF radar aurora." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape15/PQDD_0013/NQ32314.pdf.
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Palmer, Jonathan Richard. "Plasma density variations in the aurora." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262167.
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Lind, Frank David. "Passive radar observations of the aurora /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/6819.
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McIntyre, Patrick. "Targeting the Aurora-A/TPX2 interaction." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/40901.
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The mitotic serine/threonine kinase Aurora-A and its partner protein TPX2 are both overexpressed in many different cancers. It has been proposed that they work together as an oncogenic holoenzyme. TPX2 is responsible for the activation and localisation of Aurora-A during mitosis, thereby ensuring proper cell division. Disruption of the Aurora-A/TPX2 interface is therefore a potential target for novel anti-cancer drugs that exploit the increased sensitivity of cancer cells to mitotic stress. This study focuses on further characterisation of the Aurora-A/TPX2 interaction and the application of multiple approaches to developing inhibitors of Aurora-A and its complex with TPX2. We identify three key hot-spot sites within the interaction. We also reveal a previously unknown functional role within the complex for the first six residues of TPX2 and the tolerance of its flexible linker region to mutation and shortening. We show that TPX2 binds to phosphorylated Aurora-A with an order of magnitude greater affinity and provide evidence for our model of how the phosphorylation state of Aurora-A is ‘signaled’ to TPX2. To aid ongoing drug discovery efforts to inhibit Aurora-A, we show the crystal structures of several ATP-competitive inhibitors bound to Aurora-A and explain the structural mechanisms behind their high selectivity for Aurora-A. We show an alternative approach to allosterically inhibiting Aurora-A; through the use of a hydrocarbon-stapled peptidomimetic of TPX2. This stapled peptide binds to Aurora-A with a greater affinity than its wild- type, recombinantly expressed analogue and activates Aurora-A autophosphorylation to the same extent. Finally, we describe our work to develop a small molecule inhibitor of the Aurora-A/TPX2 interaction using fragment-based drug design. Following a high-throughput X-ray crystallography- based fragment screen we identified many fragment hits that bound within the Aurora-A/TPX2 binding interface. Our top fragments show inhibition of Aurora- A kinase activity, inhibition and activation of Aurora-A autophosphorylation and weaken the affinity between Aurora-A and TPX2 in competition assays.
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Lorenzon, Arthur Francisco. "Aurora : seamless optimization of openMP applications." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/179828.
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A exploração eficiente do paralelismo no nível de threads tem sido um desafio para os desenvolvedores de softwares. Como muitas aplicações não escalam com o número de núcleos, aumentar cegamente o número de threads pode não produzir os melhores resultados em desempenho ou energia. No entanto, a tarefa de escolher corretamente o número ideal de threads não é simples: muitas variáveis estão envolvidas (por exemplo, saturação do barramento off-chip e sobrecarga de sincronização de dados), que mudam de acordo com diferentes aspectos do sistema (por exemplo, conjunto de entrada, micro-arquitetura) e mesmo durante a execução da aplicação. Para abordar esse complexo cenário, esta tese apresenta Aurora. Ela é capaz de encontrar automaticamente, em tempo de execução e com o mínimo de sobrecarga, o número ideal de threads para cada região paralela da aplicação e se readaptar nos casos em que o comportamento de uma região muda durante a execução. Aurora trabalha com o OpenMP e é completamente transparente tanto para o programador quanto para o usuário final: dado um binário de uma aplicação OpenMP, Aurora o otimiza sem nenhuma transformação ou recompilação de código. Através da execução de quinze benchmarks conhecidos em quatro processadores multi-core, mostramos que Aurora melhora o trade-off entre desempenho e energia em até: 98% sobre a execução padrão do OpenMP; 86% sobre o recurso interno do OpenMP que ajusta dinamicamente o número de threads; e 91% quando comparado a uma emulação do feedback-driven threading.Efficiently exploiting thread-level parallelism has been challenging for software developers. As many parallel applications do not scale with the number of cores, blindly increasing the number of threads may not produce the best results in performance or energy. However, the task of rightly choosing the ideal amount of threads is not straightforward: many variables are involved (e.g. off-chip bus saturation and overhead of datasynchronization), which will change according to different aspects of the system at hand (e.g., input set, micro-architecture) and even during execution. To address this complex scenario, this thesis presents Aurora. It is capable of automatically finding, at run-time and with minimum overhead, the optimal number of threads for each parallel region of the application and re-adapt in cases the behavior of a region changes during execution. Aurora works with OpenMP and is completely transparent to both designer and end-user: given an OpenMP application binary, Aurora optimizes it without any code transformation or recompilation. By executing fifteen well-known benchmarks on four multi-core processors, Aurora improves the trade-off between performance and energy by up to: 98% over the standard OpenMP execution; 86% over the built-in feature of OpenMP that dynamically adjusts the number of threads; and 91% over a feedback-driven threading emulation.
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Nyman, Jeremia. "High Speed IO using Xilinx Aurora." Thesis, Linköpings universitet, Institutionen för systemteknik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-102424.
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A VHDL evaluation platform and interface to the Xilinx Aurora 8b/10b IP has been designed, tested and evaluated. The evaluation platform takes an arbitrary amount of data sources and sends the data over 1,2,4 or 8 multi gigabit serial lanes, using the Aurora 8b/10b protocol. A lightweight communications protocol for point-to-point data transfer, error detection and recovery is used to maintain a reliable and efficient transmission scheme. Priority between sources sharing the serial link is also a part of the platform. The Aurora 8b/10b IP is a lightweight protocol and transceiver interface for Xilinx FPGAs, based on the 8b/10b line encoding protocol. In addition, a demonstration PCB has been developed to introduce the Kintex-7 FPGA to future products at SAAB Dynamics.
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Dahlgren, Hanna. "Multi-spectral analysis of fine scale aurora." Doctoral thesis, KTH, Rymd- och plasmafysik, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-24907.
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The Aurora Borealis is the visible manifestation of the complex plasma interaction between the solar wind and the Earth's magnetosphere and ionosphere. Ground based and in situ measurements demonstrate a prevalence of dynamic fine structure within auroral displays, with spatial scales down to tens of metres and time variations occurring on a fraction of a second.The fine-scale morphology is related to structuring of auroral currents and electric fields and detailed spatial, spectral and temporal observations of the aurora are crucial in understanding the electrodynamic processes taking place in the ionosphere and in its coupling to the magnetosphere. In this thesis, the low-light optical instrument ASK (Auroral Structure and Kinetics) is used to image small-scale structures in the aurora at very high spatial and temporal resolution. ASK is a multi-spectral instrument, imaging the aurora in three selected emissions simultaneously. This provides information on the energy of the precipitating electrons. The SIF (Spectrographic Imaging Facility) instrument has been used in conjunction with ASK, to give a more complete picture of the spectral characteristics of the aurora, and to determine the degree of contaminating emissions present in the same spectral interval as the emission lines observed by ASK. Data from ASK and SIF are used to study the relation between the morphology and dynamics of small-scale structures in the aurora and the energy of the precipitating electrons. By comparing electron density profiles provided by EISCAT (European Incoherent SCATter) radar measurements with modeling results, information on the characteristic energy and the energy flux of the precipitating electrons can be obtained. One of the ASK channels is imaging a metastable O+ emission, which has a lifetime of about 5 s. By tracing the afterglow in this channel optically a direct measure of the E x B drift is obtained from which the local ionospheric electric field can be calculated. ASK data has also been used to analyse the properties of a distorted auroral arc, in which auroral structuring was found to take place simultaneously at different spatial scales. The smallest features, 'ruffs', are undulations found to develop on the edge of an auroral curl, fold or shear. Detailed optical studies of black aurora, including both the type which is associated with plasma shear motions and no or weak shear motions were conducted from ASK data, to investigate the spectral properties and fine scale morphology of the black structures and to shed light on the processes behind this phenomenon.QC 20101001
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Douglas, M. E. "Regulation of cytokinesis by aurora B kinase." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598609.
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In the first part of this thesis, I identify 14-3-3 protein as an interaction partner of an Aurora-phosphorylated region of MKLP1, the kinesin component of centralspindlin. I show that MKLP1 contains a highly conserved amino acid motif that encompasses a known Aurora B phosphorylation site, S708, and binds 14-3-3 when phosphorylated at a conserved serine, S710. Aurora-mediated phosphorylation of S708 inhibits binding of 14-3-3 to MKLP1. Given that S708-phosphorylated MKLP1 (which cannot bind 14-3-3) becomes highly enriched at the central spindle during anaphase, whereas S710-phosphorylated MKLP1 (which can bind 14-3-3) does not, these results suggest that Aurora B regulates centralspindlin by controlling the binding and release of 14-3-3 at different subcellular structures during cell division. Finally, I investigate whether regulated binding of MKLP1 to 14-3-3 is required for centralspindlin function and cytokinesis. I show that the sole function of Aurora-mediated S708 phosphorylation is the removal of 14-3-3 that is bound to MKLP1, and that this is required for stable binding of MKLP1 to the central spindle. 14-3-3 is necessary and sufficient to prevent the assembly of centralspindlin into higher order multimers that are known to be required for centralspindlin to bind and bundle microtubules. Collectively, these findings show that Aurora B regulates cytokinesis by releasing MKLP1 from 14-3-3 protein, enabling centralspindlin to assemble into higher order multimers that bind and bundle microtubules into the central spindle.
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Lopes, Dayara Pereira. "Aurora do Tocantins – TO : turismo e sustentabilidade." reponame:Repositório Institucional da UnB, 2018. http://repositorio.unb.br/handle/10482/34080.
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Dissertação (mestrado)—Universidade de Brasília, Centro de Excelência em Turismo, Programa de Pós-Graduação em Turismo, 2018.Esse trabalho traz à luz a discussão sobre o desenvolvimento do turismo e da sustentabilidade, tendo como objeto o município de Aurora do Tocantins e o incremento do turismo na Cidade. Buscou-se identificar, a partir da presente pesquisa, a relação entre turismo e sustentabilidade e quais dimensões desse conceito estariam presentes no modelo de desenvolvimento turístico ali desenvolvido. Buscou-se, também, identificar qual o olhar da comunidade sobre o tema. Metodologicamente, nosso estudo está amparado em pesquisa bibliográfica; pesquisa documental; trabalho de campo, com observação participante; entrevistas; e registro de imagens. Os resultados mostram que o turismo que vem se desenvolvendo em Aurora do Tocantins ainda não possui base sustentável e já começa a sinalizar para alguns efeitos negativos, principalmente no aspecto ambiental. Por essa razão, nosso estudo aponta para a necessidade de intervenção no modelo do turismo praticado no município, por meio de estudos que possibilitem a aplicação do conceito de sustentabilidade no seu desenvolvimento.
This work brings the discussion about the development of tourism and sustainability, having as object the municipality of Aurora do Tocantins and the increase of tourism in the city. From the study, the relationship between tourism and sustainability was identified, as well as the dimensions of this concept and the community's view on the theme. Methodologically, our study is supported by bibliographic research; documentary research; fieldwork with participant observation; interviews; and images registration. The results shows that the tourism that has been developing in Aurora do Tocantins still does not have a sustainable basis and already begins to signal for some negative effects, mainly in the environmental aspect. Thus, it is observed that tourism in the municipality requires intervention, through studies that make possible the application of sustainability.
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Zani, Ricardo. "O carnaval Buñuelesco = uma aurora ao entardecer." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/284472.
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Orientador: Adilson José RuizTese (doutorado) - Universidade Estadual de Campinas, Instituto de Artes
Made available in DSpace on 2018-08-18T04:40:29Z (GMT). No. of bitstreams: 1 Zani_Ricardo_D.pdf: 3571234 bytes, checksum: e29331768ad5f486c1e0293e33541420 (MD5) Previous issue date: 2010
Resumo: Para o cineasta Luis Buñuel as estranhezas deveriam sempre fazer parte de seus filmes. Um homem formado por contradições, assim era Buñuel, com seu menosprezo à sociedade e à religião cristã. Esta tese apresenta o argumento de que desde a realização do seu primeiro curta-metragem Um Cão Andaluz, roteirizado em parceria com Salvador Dalí, houve uma coerência de pensamento que estabeleceu para ambos um caminho a seguir. No prólogo deste filme, a metáfora de uma jovem moça tendo seu olho rasgado por uma navalha tornou-se cinematograficamente uma verdade estarrecedora e a essência de uma narrativa que transformou e codificou os preceitos surrealistas em dois únicos e universais temas, o amor e a liberdade, ao sintetizar a arte deste movimento nas questões mais caras aos participantes do grupo. Destaca-se aqui a galeria de estilos que se instalou na cinematografia de Luis Buñuel para reafirmar constantemente os traços marcantes de sua obra, dentre eles a polifonia, esclarecendo que a mesma reside em seus discursos quando estes se entrelaçam, se misturam e se completam. Nesta polifonia buñueliana se distingui o encontro de Um Cão Andaluz, Viridiana e Bela da Tarde com a pintura Angelus de Jean-François Millet para caracterizá-lo como um elemento constitutivo das reminiscências de Luis Buñuel e de Salvador Dalí. Resulta deste encontro polifônico uma mensagem comum nas obras aqui estudadas com o objetivo de expor que todos estes elementos apontam para uma relação com determinadas características medievais pesquisadas por Mikhail Bakhtin, a morte e os excrementos inseridos na renovação dos desejos sexuais do homem
Abstract: For the filmmaker Luis Buñuel the oddities should always be part of his films. A man made up of contradictions, so it was Buñuel, with his contempt for society and Christian religion. This thesis presents the argument that since the completion of his first short film Un Chien Andalou, written in collaboration with Salvador Dalí, there was a consistency of thought for both established a way forward. In the prologue of this film, the metaphor of a young girl with her eye torn by a knife has become a cinematic appalling truth and essence of a narrative that transformed and codified the precepts surrealists in two unique and universal themes, love and liberty, synthesize the art of this movement on the issues most dear to the group participants. We highlight here the style gallery which was installed in the film by Luis Buñuel to constantly reaffirm the hallmarks of his work, including polyphony, explaining that it lies in his speeches when they intertwine, blend and complement each other. This polyphony buñueliana be distinguished from the meeting Chien Andalou, Viridiana and Belle Afternoon with Angelus painting by Jean-Francois Millet to portray him as a constituent element of the remnants of Luis Buñuel and Salvador Dalí. Results of this meeting a common message in polyphonic works studied here in order to expose all these elements point to a relationship with certain medieval features surveyed by Mikhail Bakhtin, death and excrement inserted in the renewal of man's desires sexual
Doutorado
Artes Visuais
Doutor em Artes
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Jokiaho, Olli-Pekka. "Spectral modelling of molecular nitrogen in Aurora." Thesis, University of Southampton, 2009. https://eprints.soton.ac.uk/161195/.
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A custom made five panel filter mosaic window was designed, installed and operated with the HiTIES (High Throughput Imaging Echelle Spectrograph) at the Nordlysstasjonen in Svalbard, Norway (78.2025N and 15.829E). The filter provides images of the resonant scattered spectra of N+ 2 1N (0,1), (1,2), (2,3) bands and a neutral N2 2P (0,3) band. Ab initio models were created for describing the populations of vibrational and rotational energy levels in both excited and ionised N2 molecules in the ionosphere. In the rotational profiles the species are treated to be in thermal equilibrium, whereas the vibrational levels assume a non-thermal steady state time independent model. Rotational temperatures were evaluated for different auroral forms for the N+ 2 (0,2) band from the magnetic zenith and along the meridian slit in HiTIES data from winter. A clear trend in neutral temperature is found, with higher values for times of lower energy precipitation. The relationship between resonant scattering of solar photons via N+ 2 and direct emission from electron impact on N2 was evaluated qualitatively and quantitatively with HiTIES data from January-March 2007. A relationship was found that clearly indicates the emission profiles are a function of primary electron energy and solar shadow height when auroral arcs are partially sunlit during events of electron precipitation.
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Tuyama, Laura. "Ateliê da Aurora criança, mídia e imaginação." Florianópolis, SC, 2000. http://repositorio.ufsc.br/xmlui/handle/123456789/78879.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico.Made available in DSpace on 2012-10-17T20:26:25Z (GMT). No. of bitstreams: 0Bitstream added on 2014-09-25T17:52:42Z : No. of bitstreams: 1 176539.pdf: 3728239 bytes, checksum: 37522afcd2c1bdf0df078f9d5b996167 (MD5)
Esta dissertação busca situar o debate atual sobre a Internet, nos aspectos da arquitetura da rede, organizações de mídia, jornalismo on-line e comunidades virtuais. Procura também mostrar algumas experiências que envolvem o usuário na produção de publicações na web. Tal enfoque visa embasar a sistematização de um modelo para a construção de um gênero informativo/comunicativo, desde o planejamento até a implementação em um caso real, destacando-se os atores e recursos envolvidos. É relatada a experiência de concepção e produção do web site "Ateliê da Aurora: criança, mídia e imaginação".
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Khan, Jabbar. "Relationship between aurora kinase-C and cancer." Rennes 1, 2011. http://www.theses.fr/2011REN1S082.
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Aurora kinases belong to a conserved family of serine/threonine kinases key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved mainly in mitosis while Aurora-C is expressed during spermatogenesis and oogenesis and is involved in meiosis. Aurora-C is hardly detectable in normal somatic cells. However all three kinases are overexpressed in many cancer lines. Aurora-A possesses an oncogenic activity while Aurora-B does not. Here we investigated whether Aurora-C possesses such an oncogenic activity. We report that overexpression of Aurora-C induces abnormal cell division resulting in centrosome amplification and multinucleation in both transiently transfected cells and in stable cell lines. Only stable NIH3T3 cell clones overexpressing active Aurora-C formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3T3 stable cell lines overexpressing Aurora-C induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumour aggressiveness was positively correlated with the rate of kinase activity, making Aurora-C a potential anti-cancer therapeutic targetLes kinases Aurora appartiennent à une famille très conservée de sérine/thréonine kinases. Ces kinases sont des régulateurs clés de la progression dans le cycle cellulaire. Aurora-A et Aurora-B sont exprimées dans les cellules somatiques et sont impliquées principalement en mitose. Aurora-C, en revanche, est exprimée au cours de la spermatogenèse et de l’oogenèse et est impliquée en méiose. Aurora-C est à peine détectable dans les cellules somatiques normales. Ces trois kinases cependant sont surexprimées dans de nombreuses lignées issues de cellules cancéreuses. Aurora-A est un oncogène alors que Aurora-B ne l’est pas. Dans ce travail, nous cherchons à déterminer si Aurora-C présente aussi une activité oncogénique. Nous rapportons que la surexpression d’Aurora-C induit une division cellulaire anormale résultant en une amplification des centrosomes et une multinucléation à la fois dans les cellules transfectées transitoirement et dans les lignées stables surexprimant Aurora-C. Seuls les clones stables de cellules NIH3T3 surexprimant Aurora-C active sont capable de former des colonies en agar mou, indiquant qu’un gain d’activité d’Aurora-C est suffisant pour transformer des cellules. De plus, nous rapportons que les clones stables de cellules NIH3T3 surexprimant Aurora-C active sont capable d’induire une formation de tumeur quand ces cellules sont injectées dans des souris immuno-compromises, démontrant l’activité oncogénique d’Aurora-C enzymatiquement active. Finalement, nous trouvons que l’aggressivité des tumeurs est positivement corrélée au taux d’activité kinase d’Aurora-C. Nos travaux posent Aurora-C en tant que bonne cible potentielle thérapeutique pour le traitement de cancers
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Backman, Jonathan, and Simon Israelsson. "The Systematic Variability of Europa’s Oxygen Aurora." Thesis, KTH, Skolan för elektro- och systemteknik (EES), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-200612.
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Vacková, Markéta. "Vliv fúze na hodnotu Lázní Aurora, s.r.o." Master's thesis, Vysoká škola ekonomická v Praze, 2014. http://www.nusl.cz/ntk/nusl-262386.
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The objective of this thesis is to determine value of the Spa Aurora after the merger with Berta´s spa by DCF method and synergistic effect of the merger. The thesis is devided into the theoretical and the practical part. The theory focuses on theoretical and methodological resources for the practical part. It deals with the company appraisement, strategic and financial analysis, appraisement methods and merger. Single companies and project of the merger are introduced by the pratical part. Strategic analysis focuses on micro and macroenviroment impacts on the spa companies. Financial analysis is done using the absolute and relative indicators. Financial plans of the both spa´s and acquiring company were created for the appraisement needs. The final step is comapines appraisal by DCF method and determination of the synergistic effect of the merger. In conclusion, the major outcomes are summarized.
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Mora, Eduardo Daniel. "Aurora Consulting Firm, LLC A Business Plan." Thesis, California State University, Long Beach, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10604112.
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The healthcare industry is going through many changes. As we progress with technology, medicine, strategies, the current healthcare facilities will also need to be updated. In 1946, the first year of the baby boomer generation, it was noted that the time would come when they would retire and look for ways to have their healthcare needs met. With the recent recession, it made building new nursing homes very difficult. Aurora aims to provide services for the renovation and development of healthcare facilities that need to create or acquire space to meet the industry demand.
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Lehto, Tobias. "Aurora : Technology made to make things easier." Thesis, Blekinge Tekniska Högskola, Sektionen för teknokultur, humaniora och samhällsbyggnad, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-1564.
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Det började faktiskt redan hösten 2004, när jag satt och arbetade med ett av de otaliga projekt man gör under sin skolgång. Projektet gick ut på att skapa en hemsida med en digital katalog, och voilá, där föddes idén. Sedan fortsatte jag att fundera, vända och vrida på idén, ett system för att skapa digitala kataloger och mindre presentationer som vemsomhelst skulle kunna använda. Just detta att inte exkludera de som inte kan ”Flash” från de som skall kunna redigera systemet har varit en av mina stora grundpelare, ett slags digital demokratitanke. För att skapa systemet har jag använt ”Macromedia Flash MX” och dess inbyggda programmeringsspråk ”ActionScript”. Programmeringsspråket är inte ursprungligen tänkt att användas för att göra system, men jag tycker personligen att jag lyckats bevisa att det fungerar även för det ändamålet. Jag har även använt 3d- modelleringsprogrammet ”Alias Wavefront Maya 6.0” för att skapa viss grafik i en av systemets demonstratorer, detta för att visa på systemets potential. Under projektet har jag försökt att hela tiden tänka enkelt och utveckla ett stabilt system med stor potential. Slutprodukten har blivit mycket mer än bara ett system, det är lika mycket en vision om en framtid där fler kan använda sig av den digitala teknologin för att synas.Detta är en reflektionsdel till en digital medieproduktion.
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Santos, Edmilson Ozorio dos. "Investigação das quinases Aurora A e Aurora B como potenciais alvos terapêuticos no câncer de pulmão induzido pelo oncogene KRAS." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-15012014-143156/.
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As alterações genéticas mais frequentes em tumores de pulmão são mutações pontuais que ativam o oncogene KRAS. Apesar destas mutações estarem ligadas à oncogênese de forma causal, diferentes abordagens para inibir as proteínas RAS diretamente fracassaram na clínica. Portanto, para que melhores alvos terapêuticos para o câncer de pulmão se tornem disponíveis, será necessário identificar as vias sinalizadoras ativadas pela proteína KRAS, que são críticas para a oncogênese. O objetivo deste projeto foi identificar novos alvos terapêuticos na oncogênese pulmonar induzida pela KRAS. Este projeto se baseou na seguinte hipótese: (1) a KRAS oncogênica leva à ativação das quinases mitóticas Aurora A e/ou B e (2) que as quinases Aurora A e/ou B são alvos terapêuticos relevantes no câncer de pulmão induzido pelo oncogene KRAS. Esta hipótese foi formulada com base em estudos anteriores mostrando que a quinase Aurora A fosforila diretamente componentes das vias efetoras de RAS, e que a Aurora A e Aurora B cooperam com a RAS oncogênica na transformação maligna. Para testar esta hipótese, nós inicialmente determinamos se a forma oncogênica da KRAS induz a expressão das quinases Aurora A e B. Para tanto, nós usamos 3 modelos celulares: (1) uma linhagem primária epitelial pulmonar imortalizada e seu par isogênico transformado pela KRAS oncogênica; (2) células tumorais pulmonares H1703 manipuladas geneticamente para expressar a forma oncogênica da KRAS de forma induzível; e (3) células de adenocarcinoma pulmonar portadoras de mutações oncogênicas em KRAS H358 e A549 manipuladas geneticamente para expressar short hairpin RNAs (shRNAs) para KRAS de forma induzível. Em todos os casos, a expressão da forma oncogênica da KRAS se correlacionou positivamente com a expressão de Aurora A e B. Para validar as quinases Aurora A e B como alvos relevantes do ponto de vista terapêutico, nós usamos, nas células mencionadas acima, abordagens genéticas ou farmacológicas para inibir a expressão ou atividade das quinases Aurora A e B. Nas células A549 e H358, portadoras da forma oncogênica da KRAS, a inibição da expressão das quinases Aurora A ou B por interferência de RNA de forma induzível, bem como o tratamento com um inibidor dual destas quinases, reduziu o crescimento, viabilidade e tumorigenicidade celulares in vitro. Mais importante do que isso, no modelo celular primário isogênico, bem como na linhagem H1703 com expressão induzível de KRAS oncogênica, a inibição farmacológica dual das quinases Aurora A e B levou a uma redução no crescimento, viabilidade e tumorigenicidade celulares de forma dependente da presença da KRAS oncogênica, sugerindo que a inibição das quinases Aurora A e B afeta especificamente células transformadas pela KRAS. Em conclusão, nossos resultados apoiam a nossa hipótese de que as quinases Aurora são alvos da KRAS oncogênica no pulmão, e sugerem a inibição das quinases Aurora como uma nova abordagem para a terapia do câncer de pulmão induzido pela forma oncogênica da KRAS.The most frequent genetic change found in lung tumors are activating point mutations in the KRAS gene, which have been causally linked to the oncogenic process. Unfortunately, different approaches to target RAS proteins for therapy have been unsuccessful. Therefore, in order to select better targets for lung cancer therapy, key cancer-relevant KRAS downstream pathways will need to be identified. The overall objective of this study was to identify novel therapeutic targets in KRAS-mediated lung cancer. This project was based on the following hypothesis: (1) KRAS activates mitotic kinases Aurora A and/or B; and (2) Aurora A and/or B are relevant therapeutic targets in KRAS-induced lung cancer. This hypothesis was formulated on the basis of published studies showing that Aurora A directly phosphorylates RAS effector pathway components, and Aurora A and B both cooperate with oncogenic RAS to promote malignant transformation. In order to test this hypothesis, we first determined whether oncogenic KRAS induces Aurora kinase expression. For that purpose, we used three different cell-based models: (1) an immortalized primary lung epithelial cell line and its isogenic KRAS-transformed counterpart, (2) H1703 lung cancer cell line engineered to express oncogenic KRAS inducibly, and (3) KRAS positive lung cancer cell lines H358 and A549 stably expressing inducible shRNAs targeting KRAS. In all cases, KRAS expression positively correlated with Aurora A and Aurora B expression. In order to validate Aurora A and/or B as therapeutically relevant KRAS targets in lung cancer, we used genetic and/or pharmacological approaches in the abovementioned cells to inactivate Aurora A or B. In KRAS positive H358 and A549 cell lines, inducible shRNA-mediated knockdown of Aurora A or B, as well as treatment with a dual Aurora A and B inhibitor, decreased growth, viability and tumorigenicity in vitro. More importantly, in the primary isogenic model and in the H1703 KRAS-inducible cell line, dual pharmacological inhibiton of Aurora A and B reduced growth, viability and tumorigenicity in an oncogenic KRAS-dependent manner. This suggests that Aurora kinase inhibition therapy can specifically target KRAS transformed cells. In conclusion, our results support our hypothesis that Aurora kinases are important KRAS targets in lung cancer and suggest Aurora kinase inhibition as a novel approach for KRAS-induced lung cancer therapy.
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Hoang, Thi My Nhung. "Survivine et Aurora B kinase, deux cibles potentielles des drogues anti-mitotiques ; identification d’une nouvelle classe d’inhibiteurs des aurora kinases." Grenoble 1, 2008. http://www.theses.fr/2008GRE10007.
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Le complexe passager joue un rôle clé en mitose: contrôlant à la fois la ségrégation des chromosomes, la tension du fuseau, l'entrée en anaphase et la cytodirèse. Le complexe est composé de quatre protéines: INCENP, la kinase B, Survivine et Boréaline. Sachant que la protéine Survivine est phosphorylée par Aurora B et qu'elle a un role p sein du complexe, nous avons étudié un mutant mimant sa phosphorylation: Survivine TlI7E. La phosphoryla Survivine est nécessaire à la transition Métaphase! Anaphase. Le mutant Survivine TIl 7E est faiblement centromères en métaphase et agit comme un dominant négatif de la cytodirèse, empêchant la séparation de cellules filles. Lors de la recherche d'inhibiteurs des Aurora kinases, nous avons identifié une nouvelle classe de molécu inhibent la phosphorylation de l'histone H3 et le point de contrôle du fuseau. Ces molécules prévienr prolifération des cellules tumorales. Ces composés sont des outils intéressants pour étudier la fonction du COI passager et représentent un nouveau motif moléculaire pour le développement de drogues anti-cancéreuses. Survivine et Aurora B kinase dont l'expression est restreinte à la mitose sont deux cibles pour de nouvelles thérapies anti-mitotiquesThe chromosomal passenger complex (CPe) plays a key role in mitosis : controlling both chromosome segre spindle tension, anaphase onset and cytokinesis. The complex is composed offour proteins : INCENP, Aurora B 1 Survivin and Borealin. Taking into account that Survivin is phosphorylated by Aurora Band has a pivotaI role complex, we have studied the phosphomimetic mutant SurvivinTl 17E. Survivin phosphorylation is requir anaphase onset and the phospho-mutant is poorly linked to centromere. Moreover it exhibits a dominant 11( function in cytokinesis, preventing abscission. Ln a search for Aurora kinase inhibitors we have identified a new class of Aurora B kinase inhibitors that pl Histone H3 phosphorylation, impairs mitotic spindle checkpoint. Moreover these molecules prevent tum! proliferation. These inhibitors are interesting too]s for understanding CPC function and represent a new lead development of anti-cancer drugs. Survivin and Aurora B kinase, which are expressed exclusively in mitosis, are thus two druggable targets for ne\ mitotic therapies
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Rojanala, Sangeeta. "AURORA-A, A POTENTIAL TARGET IN PANCREATIC CANCER AND ITS STRUCTURAL ROLE IN LOCALIZATION TO THE CENTROSOMES." Diss., The University of Arizona, 2005. http://hdl.handle.net/10150/194492.
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Aurora-A kinase is overexpressed in many human cancers and leads to centrosome amplification resulting in multipolar spindles, chromosome segregation defects and aneuploidy. Aurora-A belongs to a family of serine/threonine mitotic kinases involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly. In this work, we demonstrate that Aurora-A is both amplified and overexpressed in human pancreatic cancer cell lines, with a 2-5 fold increase in gene copy number and a 3-4 fold increase in protein levels compared to controls. Aurora-A is also amplified and overexpressed in pancreatic cancers taken directly from patients. An immunohistochemistry of tissues taken directly from patients demonstrated an overexpression of Aurora-A in 26 of 28 pancreatic cancers compared to 0 of 18 normal pancreas samples. Antisense nucleotides specifically targeted at Aurora-A arrest the cell cycle in pancreatic cancer cells, indicating the potential of Aurora-A as a therapeutic target in pancreatic cancer. To understand the role of Aurora-A at the centrosome, we investigated the mechanism of how Aurora-A is targeted to the centrosome. We used deletion fragment analysis of Aurora-A to identify a specific region that is required to localize to the centrosome. We also show that subcellular localization of Aurora-A is independent of its intrinisic kinase activity and its phosphorylation states. These results show that Aurora-A is targeted to the centrosome by a mechanism that does not require its kinase activity and phosphorylation of T288 and T287. Furthermore, the region containing the catalytic domain, 131-333, is sufficient to localize Aurora-A to the centrosome.
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Zhou, Yan. "Regulation of Aurora A activity during checkpoint recovery." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181746.
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Cell division requires accurate DNA replication and cells develop checkpoint mechanisms toensure the correct passage of the genetic material. Cells arrest by a checkpoint when DNAdamage is found. After the checkpoint is silenced, the cell cycle can be resumed. Polo-likekinase 1 (Plk1) and Aurora A kinase (AurA) are both important regulators for checkpointrecovery. The question how AurA is activated was studied by many researchers, but the exactmechanism stays unclear.We developed a new setup to study AurA activation during checkpoint recovery. Quantitativeimmunofluorescence of fixed cells as well as a FRET probe that monitors Plk1 activity intime-lapse filming were applied in this study as indirect readouts of Aurora A activation. Theresult suggests that a Plk1-AurA feedback loop exists during checkpoint recovery. It can alsobe concluded that the inhibition of Cdk1 reduces Plk1 and AurA activity during checkpointrecovery. We also investigated the effect of calcium interfering drugs on AurA activation butno conclusive result was obtained.
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Yan, Ling Ling. "Building scalable and flexible mediation, the AURORA approach." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0012/NQ60042.pdf.
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Warner, Steven Lawrence. "Targeting the Aurora Kinases to Treat Pancreatic Cancer." Diss., Tucson, Arizona : University of Arizona, 2005. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1291%5F1%5Fm.pdf&type=application/pdf.
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Sindaha, Raed Yousef Saba. "Branch-level scheduling in Aurora : the Dharma scheduler." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296588.
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Johnson, Randall Lamar. "The Roycoft Inn of East Aurora, New York /." Online version of thesis, 1989. http://hdl.handle.net/1850/11306.
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Mirisola, Luiz Gustavo Bizarro. "Desenvolvimento da estação de terra do projeto AURORA." [s.n.], 2001. http://repositorio.unicamp.br/jspui/handle/REPOSIP/276535.
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Orientador : Marcel BergermanDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Computação
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Resumo: Esta dissertação apresenta o desenvolvimento da estação de terra do Projeto AURORA (Autonomous Unmanned Remote MQnitoring Robotic Airship). O objetivo do Projeto AURORA é o desenvolvimento de veículos robóticos aéreos para inspeção aérea, evoluindo de veículos puramente tele-operados para veículos telemonitorados. O protótipo da primeira fase, AURORA I, tem como finalidade a demonstração da viabilidade do projeto e a realização de missões de baixa complexidade. Esta dissertação abrange o projeto e implementação do hardware e sojtware utilizados pelo operador em terra para monitorar e controlar o vôo do dirigível. São apresentados os diversos componentes da interface com o usuário da estação de terra, o sistema utilizado para a comunicação entre a estação de terra e o sistema embarcado, e o software utilizado para se atender aos requisitos de tempo real. Adicionalmente, é apresentada a definição do sistema operacional utilizado na estação de terra e no sistema embarcado do Projeto AURORA. A estação de terra desenvolvida está sendo utilizada no Projeto AURORA, permitindo a monitoração e o envio de comandos para o dirigível em vôos reais e simulados, e fornecendo suporte para o desenvolvimento dos algoritmos de controle e do sistema embarcado do Projeto AURORA
Abstract: This dissertation shows the deveIopment of the AURORA Project's Ground Station (AURORA stands for Autonomous Unmanned Remote MQnitoring Robotic Airship). The AURORA Project aims the developement of aerial robotic vehicles to perform aerial inspection, evolving from purely teIe-operated vehicles to tele-monitored ones. The first phase prototype, AURORA l, airns to demostrate the project's viability and to accomplish low complexity missions. This dissertation presents the design and impIementation of the hardware and software used by the ground operator to monitor and control the airship flight. lt shows the various components of the useI' interface in the ground station, the communication system between the ground station and the embedded system, and the software developed to attend the real time requisites. Additionaly, it presents the definition of the operational system to be used in the Project AURORA's ground station and embedded system. The Project AURORA team is already using the developed ground station in actual and simulated flights to allow flight monitoring and to send commands to the vehicle, providing suport for the deveIopment af the controI algarithms and the embedded system
Mestrado
Mestre em Ciência da Computação
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Maeta, Silvio Mano. "Desenvolvimento da infra-estrutura embarcada do projeto AURORA." [s.n.], 2001. http://repositorio.unicamp.br/jspui/handle/REPOSIP/276495.
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Orientador : Samuel Siqueira Bueno, Maria Beatriz F. de ToledoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Computação
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Resumo: Veículos aéreos semi-autônomos não tripulados apresentam um grande potencial, ainda pouco explorado, para aplicações de pesquisa e inspeção aérea através da coleta de informações do ambiente. Tais veículos permitem que o usuário possa definir a área a ser sobrevoada, a resolução temporal e espacial dos dados que devem ser obtidos e o tipo de sensor mais adequado para cada tipo de tarefa. Contudo, o desenvolvimento deste tipo de veículo é uma atividade bastante complexa pois envolve de um lado a integração de um grande número de componentes de hardware de diferentes tipos (computadores, sensores, atuadores, link de transmissão de dados) e por outro lado o desenvolvimento do software responsável por realizar em tempo real tanto a comunicação destes dispositivos quanto o seu uso para o controle e navegação do veículo. A definição e estabelecimento de uma arquitetura, tanto de hardware quanto de software, é o elemento básico para se realizar o desenvolvimento de uma infra-estrutura integrada adequada, capaz de suportar a operação autônoma do veículo robótico. O objetivo desta dissertação é apresentar o desenvolvimento da infra-estrutura embarcada do Projeto AURORA, que visa o desenvolvimento de dirigíveis não tripulados, com elevados graus de autonomia, para aplicações de inspeção aérea. Esta dissertação aborda: os elementos de hardware utilizados no sistema embarcado; as soluções encontradas para se realizar a integração dos mesmos e; o software embarcado, responsável por realizar o tratamento de dados sensoriais, a geração de comandos para atuadores e que, também, provê o suporte para o desenvolvimento, testes e validação de algoritmos de controle e navegação. O desenvolvimento de software foi feito utilizando-se as mais modernas técnicas de engenharia de software, que permitiram um processo acelerado de implementação e testes. A infra-estrutura desenvolvida foi validada através de vôos reais, onde o dirigível era controlado remotamente e também através de vôos semi-automáticos. Os dados de telemetria, além de permitirem o acompanhamento em tempo real dos vôos também foram utilizados em uma análise posterior, validando o correto funcionamento do sistema embarcado do dirigível. A principal contribuição desse trabalho foi o desenvolvimento de um sistema embarcado próprio para ser utilizado em sistemas robóticos autônomos, validado experimentalmente através da utilização em condições reais de operação. Os resultados mais relevantes são: sistema embarcado próprio para o desenvolvimento de sistemas robóticos autônomos, o que inclui a definição do hardware e a integração dos diversos sensores embarcados; software embarcado de tempo real dedicado e; infra-estrutura de simulação para a realização de testes dos algoritmos de controle e navegação
Abstract: Unmanned semi-autonomous aerial vehicles present a great and unexplored potential in aerial inspection and research, collecting data &om the environment. Such vehicles allow the user to define the region that must be monitored, data spatial and temporal resolution in which the data must be acquired, and the most adequate type of sensor for each kind of mlSSlon. However, the development ofsuch kind ofvehicle is a very complex task because it involves on one hand the integration of a great number of different hardware devices (computers, sensors, actuators, data transmission link), and on the other hand the development of the software responsible for executing, in real-time, the communication between these devices, and also for providing the control and navigation capability for the vehicle. The definition and the establishment of an architecture, both hardware and software, is the basic element to do the development of an adequate integrated intTastructure, capable of supporting the autonomous operation of the robotic vehicle. The main objective of this text is to present the developrnent of the ernbedded infrastructure of AURORA's Project, which aims at the development of unmanned airships with high autonomy levels for aerial inspection applications. This text covers the following subjects: hardware devices used in the embedded system; solutions to integrate these devices; and also the embedded software, which in responsible for the treatrnent of sensorial data, generation of commands for the actuators and, also, to provide an environment for the development, test and validation of the control and navigation algorithms. The software development was realized using the most modero software engineering techniques, which allowed an accelerated process of implementation and tests. The validation of the developed infrastructure was made in real flights in which the airship was remotely controlled and also through semi-automatic flights. The collected telemetry data allowed the observation of the flights in real-time and also were used in a posterior analysis, validating the correct functioning of the airship's embedded system. The main contribution of this work was the development of an embedded system appropriate to be used in autonomous robotic systems, which was validated experimentally in real operation conditions. The most relevant results are: a suitable ernbedded system for the development of autonomous robotic systems, including the definition of the embedded hardware and integration of the ernbedded sensors; a dedicated real-time embedded software and; simulation infrastructure that allows the test of control and navigation algorithms
Mestrado
Mestre em Ciência da Computação
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Leibowitz, Mark Harold. "Aurora : a gene essential for mitosis in Drosophila." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46409.
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Scalabrini, Luiza Coimbra. "O papel da quinase Aurora A na biologia das células iniciadoras de turmor pulmonares com mutação em KRAS." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-11042017-082202/.
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Mutações ativadoras no gene KRAS são prevalentes em cancer de pulmão e a as vias de sinalização de RAS estão aumentadas em células iniciadoras de tumor (CITs), que são definidas como células autorrenováveis capazes de iniciar a formação tumoral, sustentar o crescimento tumoral e promover a disseminação tumoral. Entretanto, terapias direcionadas a RAS não foram efetivas até hoje e a identificação de alvos de KRAS que contribuam para o fenótipo oncogênico é necessária. Como a quinase Aurora A (AURKA) já foi implicada, tanto na oncogênese induzida por KRAS, quanto em promover a função das CITs, nós hipotetizamos que a inibição das vias de AURKA seria detrimental para a função de CITs pulmonares portadoras de KRAS oncogênica, desta forma diminuindo o comportamento maligno do câncer de pulmão. Para avaliar a função das CITs, nós usamos ensaios de crescimento de tumoresferas que permitem o crescimento seletivo de CITs in vitro. As linhagens pulmonares positivas para KRAS H358 e A549 formaram tumoresferas em cultura de baixa aderência e, quando comparadas às linhagens parentais, às células oriundas de tumoresferas apresentaram maior capacidade clonogênica in vitro e maior tumorigenicidade in vivo. Além disso, uma análise por qPCR revelou que as células oriundas de tumoresferas possuem expressão aumentada de fatores de células tronco, uma característica de CITs. Em seguida, nós inibimos a AURKA nas linhagens pulmonares positivas para KRAS H358 e A549 por interferência de RNA (RNAi) ou com um inibidor das quinases Aurora (AI II). A inibição de AURKA diminuiu a formação de tumoresferas e o crescimento destas em culturas seriadas, além de reduzir a capacidade clonogênica das células oriundas de tumoresferas. Estes resultados indicam que a AURKA é importante para a autorrenovação e a oncogenicidade de CITs, e que a AURKA induz o fenótipo tronco-tumoral, o que é corroborado pelo achado de que a inibição de AURKA nas tumoresferas reduz a expressão de fatores de célula tronco. Um destes fatores regulados por AURKA é o marcador de superfície de célula tronco CD24. De fato, quando comparadas às células cultivadas de forma aderente, as células oriundas de tumoresferas apresentam maior número de células positivas para CD24 (CD24+) e estes números são reduzidos pelo tratamento com AI II. Finalmente, nós purificamos células H358 CD24+ por citometria de fluxo e mostramos que, quando comparadas às células negativas para CD24, as células CD24+ apresentam maior capacidade de formar tumoresferas em culturas seriadas, e o tratamento com AI II inibe preferencialmente a capacidade de células CD24+ de formarem tumoresferas. Nossos resultados sugerem que uma terapia baseada na inibição de AURKA pode reduzir o número e função de CITs pulmonares portadoras de KRAS oncogênica e, portanto, pode representar uma estratégia terapêutica atraente para reduzir a recidiva e metástase no câncer de pulmão induzido por KRAS.Activating mutations in KRAS are prevalent in lung cancer and RAS sinaling is enhanced in cancer initiating cells (CICs), which are defined as self-renewing tumor cells able to initiate tumor formation, sustain tumor growth and drive tumor dissemination. However, therapies targeted to oncogenic RAS have been ineffective to date and identification of KRAS targets that impinge on the oncogenic phenotype is warranted. Because Aurora kinase A (AURKA) has been implicated both in RAS oncogenesis and in promoting CIC function, we hypothesized that targeting AURKA pathways would impair KRAS-positive lung CIC function, thereby decreasing lung cancer malignant behavior. To evaluate CIC function, we used tumorsphere assays that allow selective growth of CICs in vitro. KRAS positive lung cancer H358 and A549 cells formed tumorspheres under low attachment conditions, and, when compared to the parental cell lines, sphere-forming cells had increased clonogenic ability in vitro and increased tumorigenicity in vivo. In addition, qPCR analysis revealed that tumorsphere cells displayed increased expression of stem cell factors, a hallmark of CICs. Next, we targeted AURKA in KRAS positive lung cancer H358 and A549 cells by RNA interference (RNAi) or with an Aurora inhibitor (AI II). AURKA targeting decreased tumorsphere formation and growth in serial cultures and reduced clonogenic growth of tumorsphere-forming cells. These results indicate that AURKA is important for CIC selfrenewal and oncogenicity and that AURKA induces a CIC phenotype, which is further underscored by the finding that AURKA targeting in tumorspheres decreases expression of stem cell factors. One such factor shown to be regulated by AURKA is the stem cell surface marker CD24. In fact, when compared to adherent cultures, A549 and H358 tumorspheres display increased numbers of CD24-positive (CD24+) cells and these numbers are reduced by AI II treatment. Finally we purified H358 CD24+cells by flow cytometry and showed that, when compared to CD24-negative cells, CD24+ cells have increased ability to form tumorspheres in serial cultures, and AI II treatment preferentially reduced the ability of CD24+ cells to form tumorspheres. Our results suggest that AURKA inhibition therapy can reduce the number and function of KRAS-positive lung CICs, and, therefore might be an attractive therapeutic strategy to reduce recurrence and metastasis in KRAS-induced lung cancer.
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Mohan, Pooja. "Modification of RHAMM and TPX2 optimizes Aurora kinase A (AURKA) inhibition in malignant peripheral nerve sheath tumours." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44345.
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Malignant peripheral nerve sheath tumours (MPNST) are rare, hereditary cancers associated with neurofibromatosis type I. MPNSTs lack effective treatments as they often resist chemotherapies and have high rates of disease recurrence. Published analysis of copy number variation identified hemizygous loss of Hyaluronan Mediated Motility Receptor (HMMR, encodes RHAMM) in half of the examined high-grade MPNST, but not in benign neurofibromas or low grade tumours. RHAMM is a molecular brake for the mitotic kinase Aurora A (AURKA), so this loss of HMMR in high-grade MPNST may cause tumours to rely on AURKA activity and sensitizes them to aurora kinase inhibitors (AKI).
Three MPNST cell-lines were profiled for the expression and activity of AURKA, as well as their responses to three AKI. The sensitivity of cell-lines with amplification of AURKA was reliant upon kinase activity, which correlated with the expression of the regulatory gene products TPX2 and RHAMM. Silencing of RHAMM, but not TPX2, increased AURKA activity and sensitized MPNST cells to AKI. All three AKIs reduced kinase activity in a dose-dependent manner, and AKI treatment induced cellular responses such as apoptosis, endoreduplication and cellular senescence. Additionally, two primary human MPNSTs grown in vivo as xenotransplants were treated with the AURKA-specific inhibitor MLN8237. Treatment resulted in tumour cells exiting the cell cycle and undergoing endoreduplication, which cumulated in stabilized disease.
The MPNST cell-line S462 has a population of tumorigenic stem-like cells that can be grown in sphere culture. AURKA activity was critical to the propagation and self-renewal of sphere-enriched MPNST stem-like cells. AKI treatment significantly reduced the formation of spheroids, attenuated the self-renewal of spheroid forming cells, and promoted their differentiation. Silencing of TPX2 decreased AURKA activity, while silencing of RHAMM was sufficient to endow MPNST cells with an ability to form and maintain sphere culture. Collectively, our data indicate that AURKA is a rationale therapeutic target for MPNST, and tumour cell responses to AKI, which include differentiation, are modulated by the abundance of RHAMM and TPX2.
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Dahlgren, Hanna. "Fine-scale morphology and spectral characteristics of active aurora." Licentiate thesis, Stockholm : Electrical Engineering, Elektrotekniska system, Kungliga Tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4745.
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Noujaim, Michael. "The role of microtubules in Aurora-B's kinase activity." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107846.
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Cell division is the process by which a single cell divides into two daughter cells. Each of these two daughter cells must inherit one complete copy of the genome. If not, cancer or cell-death occurs. Not surprisingly, then, life has evolved mechanisms for ensuring that cell division is error-free. The mechanisms, broadly termed "checkpoints," prevent cell division from occurring if mistakes arise or if each daughter cell were not to inherit one copy of the genome. A major molecule involved in regulating the cell division checkpoint is called Aurora-B. Aurora-B can be thought of as a police officer--Aurora-B stops the cell division process whenever mistakes arise and corrects them before allowing cell division to continue. Unfortunately, if Aurora-B itself becomes faulty or error-prone, the police officer is off-duty, and a greater number of errors occur during cell division. For this reason, Aurora-B is commonly found to be aberrant in tumor cells. Consequently, Aurora-B has recently emerged as a main target for a vast range of novel anti-cancer drugs. In order to divide the genome properly, the cell builds a special mechanical scaffold, reminiscent of the scaffolds at construction sites, called the mitotic spindle. The building blocks of this scaffold are called microtubules. Microtubules are also a target of anti-cancer therapies. Aurora-B interacts with these microtubules in order to perform its role properly. Although significant, this interaction remains elusive for the most part. Here we provide experimental evidence for the importance of these interactions at the spindle midzone during anaphase. Using in vitro kinase assays we show that microtubules sequester Aurora-B's activity to ensure the efficiency with which crucial microtubule-associated substrates are phosphorylated at the spindle midzone. Thus, allowing the unhindered progression of anaphase and the completion of cytokinesis.La division cellulaire est le processus par lequel une cellule se divise en deux cellules filles. Chacune de ces cellules filles doivent hériter d'une copie complète du génome. Sinon, cela mène à la mort cellulaire ou au cancer. Ainsi, il n'est pas surprenant que la vie a fait évoluer des mécanismes pour s'assurer que la division cellulaire est dénuée d'erreurs. Ces mécanismes, appelés « points de contrôle », empêchent la division cellulaire de se produire si des erreurs apparaissent ou si chaque cellule fille n'a pas hérité d'une copie complète du génome. Une molécule exerçant un rôle majeur dans la régulation du point de contrôle du cycle cellulaire est appelée Aurora-B. Son rôle est en quelque sorte analogue à celui d'un officier de police – Aurora-B arrête la division cellulaire dès que des erreurs surviennent et les corrige avant de permettre à la division cellulaire de continuer. Malheureusement, si Aurora-B devient défectueux ou sujet à des erreurs, l'officier de police est hors-service, alors un plus grand nombre d'erreurs peuvent survenir pendant la division cellulaire. Pour cette raison, Aurora-B est fréquemment identifié comme étant aberrant dans les cellules tumorales. Conséquemment, Aurora-B a récemment émergé en tant que cible principale pour une vaste gamme de nouveaux médicaments anti-cancer. Afin de diviser le génome correctement, la cellule construit un échafaudage mécanique spécial, qui rappelle les échafaudages retrouvés dans les chantiers de construction, qu'on appelle le fuseau mitotique. Les morceaux constituant cet échafaudage sont appelés microtubules. Les microtubules sont aussi une cible de certaines thérapies anti-cancer. Aurora-B interagit avec ces microtubules afin d'exécuter son rôle correctement. Malgré le caractère significatif de cette interaction, elle demeure nébuleuse en bonne partie. Nous fournissons donc ici des preuves expérimentales de l'importance de ces interactions dans la zone médiane du fuseau pendant l'anaphase. En utilisant des essais kinase in vitro, nous montrons que les microtubules séquestrent l'activité d'Aurora-B afin d'assurer l'efficacité avec laquelle les substrats associés aux microtubules sont phosphorylés dans la zone médiane du fuseau. Ainsi, cela permet une progression sans entrave de l'anaphase et la fin de la cytocinèse.
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Kotwaliwale, Chitra V. "Regulation and functions of the Ipl1/aurora protein kinase /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/5081.
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Lüer, Edwin. "Aurum und Aurora Ludwig Tiecks Runenberg und Jakob Böhme /." Heidelberg : C. Winter, 1997. http://catalogue.bnf.fr/ark:/12148/cb37037084h.
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He, Lili. "Molecular Mechanism of Aurora-A Kinase in Human Oncogenesis." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002582.
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